It is known that glutamic acid released from the presynaptic region plays an important role in excitatory signaling in the central nervous system. This action is brought about when glutamic acid binds to glutamate receptors present in the postsynaptic region, and the glutamate receptors are classified into ionotropic receptors and G-protein-coupled receptors, with the former being further classified into α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, N-methyl-D-aspartic acid (NMDA) receptor, kainate receptor, and the like. Among the above, the AMPA receptor is a receptor that is widely expressed in the brain, and plays a key role in the regulation of fast excitatory synaptic transmission or synaptic plasticity.
Since the AMPA receptor thus plays a physiologically important role, its dysfunction is known to be involved in various diseases, for example, by causing abnormal excitability of neurons where the AMPA receptor is present. Examples of such diseases include epilepsy, various pains (peripheral nerve pain, central nerve pain, and nociceptive pain (each including chronic, acute, or intermittent pain)), various demyelinating diseases such as multiple sclerosis, various neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Huntington's chorea, and AIDS neuropathy, various psychiatric diseases such as anxiety, depression, bipolar mood disorder, dependency, drug abuse, and schizophrenia, motor dysfunction such as cerebral ischemia, head trauma, cerebrospinal injury, tremor, dystonia, and dyskinesia, and a developmental disorder such as autism. Inhibitors of the AMPA receptor (AMPA inhibitors) are therefore expected to lead to the treatment of these diseases, and are particularly known to be useful in treating epilepsy (Non Patent Literature 1).
Epilepsy is one of the most frequent central nerve diseases, and there are about 50 million or more epileptic patients worldwide. According to the World Health Organization, epilepsy is defined as “a chronic disorder of the brain caused by various causes; it is mainly characterized by recurrent seizures (epileptic seizures) derived from excessive electrical discharges in cerebral neurons, and the seizures involve manifestations of clinical and examination findings that vary greatly”.
Examples of known epileptic seizures include partial seizures such as simple partial seizure, complex partial seizure, and secondary generalized seizure, absence seizure, myoclonic seizure, clonic seizure, tonic seizure, tonic-clonic seizure, atonic seizure, tuberous sclerosis complex, Dravet syndrome, progressive myoclonic epilepsy, Lafora disease, Unverricht-Lundborg disease, dentatorubral-pallidoluysian atrophy, fragile X syndrome, West syndrome, and Lennox-Gastaut syndrome. Epilepsy treatment is based on pharmacotherapy with anti-epileptic drugs. The goal of epilepsy treatment is to eliminate epileptic seizures, and avoid the development of side effects caused by the treatment. Treatment with anti-epileptic drugs begins with a single drug in principle. Generally, single-drug treatment is carried out by sequentially using two or three different drugs, and if this is not successful, multiple drug treatment is attempted. Amelioration of seizures through the treatment with anti-epileptic drugs can be expected in about 70% of patients with new onset of epilepsy. It is known, however, that in the remaining about 30% of patients, epileptic seizures are difficult to suppress even with drug treatment including multiple drug therapy.
An epileptic seizure is believed to be caused when abnormal excitability of some neurons develops into abnormal synchronization of firing in an entire population of neurons, and there have been many reports that glutamate neurons, in particular, the AMPA receptor, play a key role in the occurrence and propagation of an epileptic seizure. For example, it has been reported that AMPA inhibitors suppress the occurrence and propagation of convulsions in rat bicuculline-induced convulsion models (Non Patent Literatures 2 and 3); additionally, it is well known that AMPA inhibitors exhibit potent anticonvulsant action in a wide range of convulsion models (Non Patent Literatures 4 and 5). Further, it is known that AMPA inhibitors also have seizure-stopping action in status epilepticus models that experience extremely serious and continuous seizures, and thus, AMPA inhibitors are also expected to be applied to status epilepticus (Non Patent Literature 6).
It has been reported that similarly in humans, the expression of the AMPA receptor was increased in hippocampal neurons containing an epileptic focus, which were sampled from epileptic patients (Non Patent Literature 7). Further, because AMPA receptor inhibitors have been reported to have anticonvulsant action in humans, they are expected to have efficacy particularly as agents for treating epilepsy (Non Patent Literature 5).
As described above, AMPA inhibitors are expected to become therapeutic drugs for various central nerve diseases such as epilepsy; however, they are known to cause central nervous system depressant action such as sedation or loss of coordination, at a dose substantially equivalent to or lower than that showing main effect (Non Patent Literature 8). It has been reported that in humans, the central nervous system depressant action is reduced if the dose is gradually increased (Non Patent Literature 9); however, central nervous system depressant action is observed at a middle to high dose, which has become a problem that lowers the quality of life of epileptic patients in need of long-term administration, and also leads to the restriction of the dose.
The following compound is known as a compound having AMPA receptor inhibitory action (Patent Literature 1):

wherein A1, A2, and A3 may each independently be a C6-14 aromatic hydrocarbon cyclic group or 5- to 14-membered aromatic heterocyclic group; X1, X2, and X3 may each independently be a single bond; Q may be an oxygen atom; Z may be a carbon atom; R1 and R2 may be attached to each other such that CR2—ZR1 forms a carbon-carbon double bond represented by C═C; and R3 may be attached to any atom on A3, and together with the atom, may form an optionally substituted 5- to 8-membered heterocyclic ring.
In particular, Patent Literature 1 discloses as Example 9 a compound having a tricyclic skeleton represented by the formula:
